HBV感染肾小管细胞机制的研究进展

肾脏具备HBV感染肝细胞的关键因素,HBV相关肾小球肾炎(HBV-GN)的发病机制尚未完全明确,近年来HBV直接损伤肾小管的机制越来越受到重视。HBV可以通过调节细胞周期、激活NF-κB等相关信号转导通路诱导肾小管细胞凋亡,导致HBV-GN进展。目前在临床上尚无作用靶点位于肾脏治疗HBV-GN的药物。将HBV感染细胞的关键因素和HBV损伤肾小管细胞研究进展总结如下,阐述HBV直接感染肾小管细胞的可能机制,为HBV-GN的治疗提供新思路。     

HBV相关肾小球肾炎的研究进展

慢性HBV感染人群数量庞大,HBV不仅损害肝脏,肾脏也是主要受累器官之一,HBV相关肾小球肾炎(HBV-GN)是由HBV感染引起的继发性肾小球肾炎,是HBV感染最常见的肝外并发症之一。HBV-GN多见于儿童及中青年人,男性多见,临床上以不同程度蛋白尿为主要表现,可伴有血尿和高血压,最常见病理类型为膜性肾病,其次为系膜增生性肾小球肾炎和IgA肾病。HBV-GN起病隐匿,缺乏特征性的症状及病理学表现,易与各种肾小球肾炎混淆,导致漏诊误诊。HBV-GN发病机制复杂,涉及免疫紊乱、病毒直接损伤、遗传等诸多环节,其中免疫复合物沉积学说已得到广泛认可。近年来关于HBV-GN发病机制、诊断及治疗方面的研究取得了一些重要进展。本文将对此进行综述,希望为临床诊治提供参考。     

乙型肝炎病毒相关性肾炎患者病毒基因型及变异的临床分析

目的检测乙型肝炎病毒相关性肾炎(HBV-GN)患者的HBV基因型,探讨HBV S区、P区变异与HBV-GN病情变化的相关性。方法对10例确诊HBV-GN患者取血,抽提全基因组DNA,DNA测序仪检测HBV P区、S区序列,进行病毒基因分型,并查找突变位点。结果 10例HBV-GN患者检出HBV基因型C型9例(占90%),B型1例(占10%);出现YVDD变异1例,同义突变1例,各占10%。结论本组HBV基因型以C型为主,发生变异少,未发现HBV变异与HBV-GN病情变化的相关性。     

HBV相关性肾炎的抗病毒治疗

乙型肝炎病毒相关性肾炎(hepatitis B virus associated glomerulonephritis,HBV-GN)是HBV感染的表现之一.已有多种药物被用于治疗HBV-GN,但迄今为止尚无最佳的治疗方案.抗病毒(包括干扰素和核苷类似物)治疗HBV-GN能有效抑制HBV复制、缓解蛋白尿,且HBeAg的...     

小儿乙肝病毒相关性肾炎肾组织中病毒DNA存在状态的进一步研究

本文报道了对3例小儿乙肝病毒相关性肾炎的肾组织,应用Southcrn印迹法检测出非复制游离型HBV DNA,而在3例非HBV-GN的肾组织中则无HBV DNA。参考以往报道2例HBV-GN的肾组织中有整合型HBV DNA,提示HBV-GN的肾组织中存在HBV DNA不是偶然现象。根据以上研究,作者认为肾组织中HBV DNA如能表达,则可能是HBV抗原的来源之一,被释放后与相应抗体沉着于肾病灶中。     

HBV相关性肾炎的抗病毒治疗研究进展

HBV相关性肾炎(HBV-associated glomerulonephritis,HBV-GN)是HBV慢性感染最常见的肝外表现之一,主要表现为免疫复合物介导的肾小球疾病。这类患者情况特殊、病情复杂,通常须进行针对性的抗病毒治疗,故及时把握治疗时机以及正确选用抗病毒药物对HBV-GN治疗极为关键,但迄今为止仍无规范统一的治疗策略。本综述参考国内外最新信息,对HBV-GN的抗病毒治疗研究进展以及各抗病毒药物的疗效、安全性等进行总结,以期为临床决策提供参考。     

乙型肝炎病毒相关性肾炎的诊治现状

乙型肝炎病毒相关性肾炎(hepatitis B virus associated glomerulonephritis,HBV-GN)目前尚无公认、明确的定义。究其本质,实为继发于乙型肝炎病毒(HBV)感染、通过免疫介导的肾小球肾炎,亦即其患病的始动因素是HBV感染,特别是慢性HBV感染;通过HBV抗原(HBAg)在宿主体内形成免疫复合物(IC)致病。我国属HBV高度感染区(总感染率>60%,慢性感染率8%-16%),HBV表面抗原(HBsAg)阳性率高达9.09%,约1.2亿-1.3亿人口。慢性HBV感染并发HBV-GN约8.8%[1],按此计算     

老年乙肝病毒相关性肾炎16例临床及病理分析

我国乙型肝炎发病率较高,乙型肝炎病毒(HBV)除了可感染肝脏外,尚可累及肾脏引起HBV相关性肾炎(HBV-GN).HBV-GN为老年常见继发性肾脏疾病,临床表现多样,肾脏病理通常改变较重.老年患者由于年龄大,各器官功能较差,且大多数同时患有慢性乙型肝炎,激素及免疫抑制剂的应用受到一定程度的限制,故与年轻人和一般的肾小球肾炎治疗相比,疗程更长,效果更差.本文拟进行老年HBV-GN临床及病理的研究,旨在提高疗效,改善预后.     

黑素瘤缺乏因子2在乙型肝炎病毒相关性肾小球肾炎发病机制中的作用

目的 初步探讨黑素瘤缺乏因子2(AIM2)激活与表达在HBV相关性肾小球肾炎(HBV-GN)发病机制中的作用.方法 54例HBV-GN患者为研究组,25例慢性肾小球肾炎患者为阴性对照组,6例慢性乙型肝炎患者为阳性对照组.免疫组织化学法分别测定研究组、阴性对照组患者肾组织及阳性对照组患者肝组织中AIM2、Caspase-1、IL-1β的表达.组间比较采用卡方检验,相关性分析采用Spearman相关分析.结果 54例HBV-GN患者肾组织中AIM2的阳性表达率为81.4％,25例慢性肾小球肾炎组为4.0％,两组间差异有统计学意义(x2=38.746,P＜0.01).AIM2在6例慢性乙型肝炎患者肝组织中均有表达.HBV-GN组AIM2的表达强度与Caspase-1呈正相关(rs=0.444,P＜0.01),IL-1β的表达强度与Caspase-1也呈正相关(rs=0.515,P＜0.01).HBV-GN患者中血HBV DNA≥1×105拷贝/mL者AIM2的表达强度高于HBV DNA＜1×105拷贝/mL者(x2=6.097,P＜0.05).结论 AIM2的激活与HBV-GN有关,可能通过Caspase-1激活,释放炎性因子IL-1β.     

乙型肝炎病毒相关性肾炎中Toll样受体4沉积特点及其意义

目的 观察HBV相关性肾炎(HBV-GN)患者肾组织Toll样受体4(TLR4)的表达及分布情况,探讨TLR4与HBV-GN肾组织病变及临床表现的关系.方法 采用免疫组化法检测经肾活检确诊的48例HBV-GN患者及154例非HBV-GN患者的肾组织标本,观察肾组织TLR4的分布特征,明确TLR4与HBsAg的分布关系,结合病史资料,统计并分析其与病理类型,肾小球、肾小管病变程度,肾间质炎性细胞浸润程度及血清HBV等临床指标之间的关系.结果 TLR4以棕红色颗粒状物主要沉积在HBV-GN组患者的肾小管及间质中,且与HBsAg的分布基本一致.HBV-GN组TLR4阳性率及阳性积分均高于非HBV-GN组(P＜0.05).在系膜增生性肾小球肾炎组、局灶节段性肾小球硬化症组TLR4阳性积分略高,但差异无统计学意义(P＞0.05);肾小管病变程度与TLR4的表达显著相关(r =0.748,P＜0.001),且随肾小管萎缩、炎性细胞浸润及间质纤维化的程度加重而升高(r分别为0.577、0.684、0.569,P值均＜0.001),但与肾小球的病变程度无显著相关性(r=0.293,P=0.053).回归分析发现,TLR4表达随血压的升高、GFR的下降、高敏C反应蛋白的增加及24h尿蛋白定量的增多而增加(R2分别为0.869、0.784、0.979、0.615),其余临床指标均无统计学意义.结论 TLR4在HBV-GN肾组织中有异常表达,主要分布于肾小管上皮细胞及间质组织,其分布与HBsAg分布基本一致,表达水平与炎性细胞浸润、肾间质病变及肾功能变化密切相关.故推测,HBV-GN肾组织中的HBV可促进TLR4的异常表达,后者可能参与了HBV-GN的肾脏组织病变的进展.     

The immunoneuroendocrine role of melatonin

Abstract: A tight, physiological link between the pineal gland and the immune system is emerging from a series of experimental studies. This link might reflect the evolutionary connection between self-recognition and reproduction. Pinealectomy or other experimental methods which inhibit melatonin synthesis and secretion induce a state of immunodepression which is counteracted by melatonin. In general, melatonin seems to have an immunoenhancing effect that is particularly apparent in immunodepressive states. The negative effect of acute stress or immunosuppressive pharmacological treatments on various immune parameters are counteracted by melatonin. It seems important to note that one of the main targets of melatonin is the thymus, i.e., the central organ of the immune system. The clinical use of melatonin as an immunotherapeutic agent seems promising in primary and secondary immunodeficiencies as well as in cancer immunotherapy. The immunoenhancing action of melatonin seems to be mediated by T-helper cell-derived opioid peptides as well as by lymphokines and, perhaps, by pituitary hormones. Melatonin-induced-immuno-opioids (MHO) and lymphokines imply the presence of specific binding sites or melatonin receptors on cells of the immune system. On the other hand, lymphokines such as -γ-interferon and interleukin-2 as well as thymic hormones can modulate the synthesis of melatonin in the pineal gland. The pineal gland might thus be viewed as the crux of a sophisticated immunoneuroendocrine network which functions as an unconscious, diffuse sensory organ.     

Changes in connexin43, the gap junction protein of astrocytes, during development of the rat pineal gland

Abstract: The abundance of gap junctions between rat pineal astrocytes formed by connexin43 (Cx43) was studied during development. Levels and distribution of Cx43 were measured by immunoblotting and indirect immunofluorescence, respectively. The amount of Cx43 in cells located within the gland was low until about the 7th postnatal day and increased to adult values between the 14th and 21st days postpartum. Although astrocytes, recognized by their vimentin immunoreactivity, were scarce before birth, they were abundant by the 7th postnatal day suggesting that the low levels of Cx43 found at this age corresponded to a low expression of this protein. Localization of the immunoreactivity to Cx43 and vimentin showed a close correlation, indicating that mature or immature pineal astrocytes form gap junctions made of Cx43. Since Cx43 levels attained their adult values at about the time the innervation and the functional state of the gland reached maturity (2–3 weeks after birth), it is proposed that astrocyte gap junctions are involved in the function of the adult rat pineal gland.     

Conservative management of perforated duodenal diverticulum： A case report and review of the literature

Duodenal diverticula are a relatively common condition. They are asymptomatic, unless they become complicated, with perforation being the rarest but most severe complication. Surgical treatment is the most frequently performed approach. We report the case of a patient with a perforated duodenal diverticulum, which was diagnosed early and treated conservatively with antibiotics and percutaneous drainage of secondary retroperitoneal abscesses. We suggest this method could be an acceptable option for the management of similar cases, provided that the patient is in good general condition and without septic signs.     

Presence of immunoreactive growth hormone and prolactin in the ovine pineal gland

Abstract: The use of antisera raised against bovine growth hormone (GH) and ovine prolactin (PRL) enabled the detection of related immunoreactive (ir) sequences of proteins in ovine pineal tissue. The isolation of PRL-like ir-material was accomplished using a 0.25 M ammonium sulphate (pH 5.5) extraction followed by ethanol precipitation, whereas the resulting 2.0 M ammonium sulphate (pH 7.0) precipitate contained a GH-like immunoreactivity. Gel chromatography of the GH-like immunoreactivity (Sephadex G-100) indicated the presence of several GH-like fragments ranging in the M_r range of 7,000 to 55,000. Analyses of the PRL-like ir-material found in pineal tissue on HPLC using a TSK 545-DEAE column led to the resolution into a single peak of immunoreactivity. A single peak of activity was also observed following chromatofocusing and hydrophobic interaction chromatography of the ir-peak from the TSK 545-DEAE column. The PRL-like ir-material inhibited the binding of [¹²⁵I]ovine PRL-S14 to anti-ovine PRL antibodies without showing an affinity for binding to anti-rat PRL or anti-bovine GH antibodies. Scatchard analysis of the binding of pineal PRL-like ir-material and pituitary ovine PRL-S14 to liver membranes from day-20 pregnant rats revealed similar affinity constants (K_a of 4.7 ± 0.2 × 10⁹ M^-1). In addition, the replication of Nb 2 Node rat lymphoma cells was stimulated by pineal PRL-like ir-material, an effect known to be specific for lactogenic hormones. The pineal PRL-like immunoreactivity appeared on sodium dodecyl sulfate polyacrylamide gels as a single major band of M_r 24,000. The functional status of PRL-and GH-like ir-material in the ovine pineal remains to be determined, but evidence is presented that the overall protein synthesis rate of the rat pineal responded to circulating concentrations of PRL.     

N-acetyl-L-cysteine combined with mesalamine in the treatment of ulcerative colitis： Randomized,placebo-controlled pilot study

AIM： To evaluate the effectiveness and safety of oral N-acetyl-L-cysteine （NAC） co-administration with mesalamine in ulcerative colitis （UC） patients.
METHODS： Thirty seven patients with mild to moderate UC were randomized to receive a four-wk course of oral mesalamine （2.4 g/d） plus N-acetyl-L-cysteine （0.8 g/d） （group A） or mesalamine plus placebo （group B）. Patients were monitored using the Modified Truelove-Witts Severity Index （MTWSI）. The primary endpoint was clinical remission （MTWSI ≤ 2） at 4 wk. Secondary endpoints were clinical response （defined as a reduction from baseline in the MTWSI of ≥ 2 points） and drug safety. The serum TNF-α, interleukin-6, interleukin-8 and MCP-1 were evaluated at baseline and at 4 wk of treatment. RESULTS： Analysis per-protocol criteria showed clinical remission rates of 63% and 50% after 4 wk treatment with mesalamine plus N-acetyl-L-cysteine （group A） and mesalamine plus placebo （group B） respectively （OR = 1.71; 95% CI： 0.46 to 6.36; P = 0.19; NNT = 7.7）. Analysis of variance （ANOVA） of data indicated a significant reduction of MTWSI in group A （P = 0.046） with respect to basal condition without significant changes in the group B （P = 0.735） during treatment. Clinical responses were 66% （group A） vs 44% （group B） after 4 wk of treatment （OR = 2.5; 95% CI： 0.64 to 9.65; P = 0.11; NNT = 4.5）. Clinical improvement in group A correlated with a decrease of IL-8 and MCP-1. Rates of adverse events did not differ significantly between both groups.
CONCLUSION： In group A （oral NAC combined with mesalamine） contrarily to group B （mesalamine alone）, the clinical improvement correlates with a decrease of chemokines such as MCP-1 and IL-8. NAC addition not produced any side effects.     

Delorme's transrectal excision for internal rectal prolapse

Surgical therapy of functional outlet obstruction in patients with internal rectal intussusception may include abdominal, perineal, or transrectal procedures. Because abdominal procedures often result in significant physiologic impact but unrelieved constipation, the authors have elected Delorme's transrectal excision for management of these patients. Since a short-term placebo effect attends many therapies, this report describes results of transrectal excision only after a threeyear postoperative period. Delorme's transrectal excision of internal intussusception accomplished sustained symptomatic relief in over 70 percent of otherwise refractory constipated patients. The association of internal intussusception with other abnormalities underscores the importance of defining both anatomic and functional components when selecting patients whose constipation may require surgical therapy. Critical technical elements, surgical pitfalls, and potential complications of the procedure are discussed.Poster presentation at the meeting of The American Society of Colon and Rectal Surgeons, Toronto, Canada, June 11 to 16, 1989.     

The oral glucose tolerance test: A comparison of the time points on the basis of limit values,normal dispersion,and reproducibility

Summary Time points in the glucose tolerance test (GTT) are compared on the basis of limit values, dispersion within a reference population, and reproducibility. We suggest using the distance between a limit value and the median reference value as a measure of the magnitude of abnormality. The distance between 140 mg/100 ml and the median fasting plasma glucose value is chosen as a standard distance and limits for other points in the GTT are calculated to equal this standard distance of abnormality. We suggest that the probability of correctly interpreting an inividual result is directly related to the reproducibility of the test and inversely related to the percentage of the total range of values which is dispersed among the normal population. The ratio of reproducibility to percentage normal dispersion is proposed as an index of the probability of correctly interpreting an individual result. According to this index, the probability of correct interpretation varies in order: fasting plasma glucose concentration>3-h>2-h>0.5-h>1-h plasma glucose concentration.